The present invention relates generally to a new gene that encodes an enzyme inhibitor. In particular, the present invention relates to a novel serpin, designated xe2x80x9cZserp11,xe2x80x9d and to nucleic acid molecules encoding Zserp11.
Endogenous proteolytic enzymes provide a variety of useful functions, including the degradation of invading organisms, antigen-antibody complexes, and certain tissue proteins that are no longer necessary. The serine proteases comprise a large family of enzymes that use an activated serine residue in the substrate-binding site to catalytically hydrolyze peptide bonds. Typically, this serine residue can be identified by the irreversible reaction of its side chain hydroxyl group with diisopropylfluorophosphate. Serine proteases participate in carefully controlled processes, such as blood coagulation, fibrinolysis, complement activation, fertilization, and hormone production.
Normally, serine proteases catalyze limited proteolysis, in that only one or two specific peptide bonds of the protein substrate are cleaved. Under denaturing conditions, serine proteases can hydrolyze multiple peptide bonds, resulting in the digestion of peptides, proteins, and even autolysis. Several diseases are thought to result from the lack of regulation of serine protease activity, including emphysema, arthritis, cancer metastasis, and thrombosis.
In vivo, serine protease activity is limited by protein inhibitors. Serine protease inhibitors, or serpins, constitute a family of proteins that bind with target proteases. These inhibitors, like their protease targets, play significant roles in physiology. For example, serpin dysfunction is associated with emphysema, blood clotting disorders, cirrhosis, Alzheimer disease, and Parkinson disease (see, for example, Eriksson et al., New Eng. J. Med. 314:736 (1986); Wiebicke et al., Europ. J. Pediat. 155:603 (1996); Kamboh et al., Nature Genet. 10:486 (1995); Yamamoto et al., Brain Res. 759:153 (1997)).
The discovery of a new serine protease inhibitor fulfills a need in the art by providing a new composition useful in diagnosis, therapy, or industry.
The present invention provides a novel serpin, designated xe2x80x9cZserp11.xe2x80x9d The present invention also provides Zserp11 variant polypeptides and Zserp11 fusion proteins, as well as nucleic acid molecules encoding such polypeptides and proteins, and methods for using these nucleic acid molecules and amino acid sequences.